Continuous-flow synthesis of 7-methoxy-1-tetralone: an important intermediate of (-)-Dezocine

Continuous flow technology has been widely adopted in manufacturing active pharmaceutical ingredients (APIs). Herein, we report an expeditious multi-step continuous-flow strategy for an efficient and highly productive flow synthesis of 7-methoxy-1-tetralone, which is an essential intermediate for the opioid analgesic drug (-)-dezocine. Compared with the traditional batch operation, this work presents significant advantages of continuous-flow chemistry with dramatically reduced reaction time, highly improved reaction efficiency, good controls over reaction optimizing conditions, etc. The flow protocol in this work provided the desired product in an overall yield of up to 76.6% with 99% purity, much higher than those from batch process (i.e., 50% yield, 92% purity). Moreover, reaction efficiency is highly improved with a throughput of 0.49 g/h, the total reaction time is markedly reduced from hours in batch to minutes in flow process.